Dimethylformamide → HCID 69082194, compound

HRID 244851Notes

Reaction equation

HRID 244851 reaction equation
CN(C)C=O.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:28](#[N:31])[CH:29]=[CH2:30].[NH2:32][C:33]1[C:42]2[N:43]=[C:44]([CH2:51][O:52][CH3:53])[N:45]([CH2:46][C:47]([CH3:50])([OH:49])[CH3:48])[C:41]=2[C:40]2[CH:39]=[CH:38][C:37](Br)=[CH:36][C:35]=2[N:34]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:32][C:33]1[C:42]2[N:43]=[C:44]([CH2:51][O:52][CH3:53])[N:45]([CH2:46][C:47]([OH:49])([CH3:50])[CH3:48])[C:41]=2[C:40]2[CH:39]=[CH:38][C:37]([CH:30]=[CH:29][C:28]#[N:31])=[CH:36][C:35]=2[N:34]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7855AcrylonitrileHCID 80271Tri-o-tolylphosphineHCID 21984234HCID 21984234, compound

Product 1

HCID 69082194HCID 69082194, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (225 mg, 1.00 mmol), acetonitrile (50 mL), N,N-dimethylformamide (20 mL) triethylamine (8.25 mL, 59.3 mmol), tri-o-tolylphosphine (900 mg, 2.97 mmol), acrylonitrile (770 mg, 21.8 mmol) and 1-[4-amino-7-bromo-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (7.50 g, 19.8 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath for 18 hours. The reaction was cooled to ambient temperature and then concentrated under reduced pressure. The resulting solid was partitioned between chloroform (300 mL) and aqueous 1% sodium carbonate (100 mL). The fractions were separated and the aqueous fraction was extracted with chloroform (4×100 mL). The combined organic fractions were concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-7% gradient of methanol in dichloromethane) to provide 5.2 g of 3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enenitrile as an off-white solid.

Workup

  1. customA thick walled glass tube, equipped with a stir bar
  2. customThe reaction mixture was purged with nitrogen
  3. customthe tube was sealed
  4. temperatureThe reaction was cooled to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting solid was partitioned between chloroform (300 mL) and aqueous 1% sodium carbonate (100 mL)
  7. customThe fractions were separated
  8. extractionthe aqueous fraction was extracted with chloroform (4×100 mL)
  9. concentrationThe combined organic fractions were concentrated under reduced pressure
  10. custompurified by chromatography
  11. washa HORIZON HPFC system (silica cartridge, eluting with 0-7% gradient of methanol in dichloromethane)

Sources & evidence

ORD record
ord-916d36ee8bb149238df18168557ba501
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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